Abstract
Studies using a fungal model, Saccharomyces cerevisiae, have been instrumental in advancing our understanding of sulfur metabolism in eukaryotes. Sulfur metabolites, particularly methionine and its derivatives, induce anabolic programs in yeast, and drive various processes integral to metabolism (one-carbon metabolism, nucleotide synthesis, and redox balance). Thereby, methionine also connects these processes with autophagy and epigenetic regulation. The direct involvement of methionine-derived metabolites in diverse chemistries such as transsulfuration and methylation reactions comes from the elegant positioning and safe handling of sulfur through these molecules. In this mini-review, we highlight studies from yeast that reveal how this amino acid holds a unique position in both metabolism and cell signaling, and illustrate cell fate decisions that methionine governs. We further discuss the interconnections between sulfur and NADPH metabolism, and highlight critical nodes around methionine metabolism that are promising for antifungal drug development.
Highlights
For most researchers, methionine is invariably connected to the start of protein translation, as it is typically the first amino acid encoded in a polypeptide chain
We summarize important characteristics of methionine and methionine-derived metabolites, and highlight its roles in signaling and metabolism, as well as in translation
The host of genes regulated by methionine that were involved in metabolism could be organized into a clear hierarchy
Summary
Methionine is invariably connected to the start of protein translation, as it is typically the first amino acid encoded in a polypeptide chain. This metabolite is biochemically unique among the 20 natural amino acids. Suitable conversions of methionine to its derivatives [primarily S-adenosyl methionine (SAM)], and their connections to key metabolic and signaling pathways show that the role of methionine is not limited to the initiation of translation alone (Figures 1A,B). This minireview focuses on the role of methionine as an anabolic signal. Studies using Saccharomyces cerevisiae have revealed conserved facets of methionine-mediated effects, such as the inhibition of autophagy (Wu and Tu, 2011; Sutter et al, 2013), the regulation of tRNA thiolation, which controls overall metabolic state (Laxman et al, 2013; Gupta et al, 2019), and increased cell proliferation
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